Researchers differentiate pancreatic cancer cells into normal cells and reintroduce to animal model.
A new research study has shown that pancreatic cancer cells can be coaxed to revert back toward normal cells by introducing a protein called E47. E47 binds to specific DNA sequences and controls genes involved in growth and differentiation. The research from the Sanford-Burnham, UC San Diego and Purdue University provides hope for a new treatment approach for the more than 40,000 people who die from the disease each year in the United States.
The team state that pancreatic adenocarcinoma is the most common form of pancreatic cancer. It’s primarily caused by a mutation in the oncogene called Kras that causes the digestive enzyme-secreting cells (acinar cells) to differentiate into a destabilized duct-like cell type, which is cancerous. The disease is often called a ‘silent cancer’ because it rarely shows early symptoms, it tends to be diagnosed at advanced stages when it causes weight loss, abdominal pain, and jaundice.
For the first time a study has shown that overexpression of a single gene can reduce the tumour-promoting potential of pancreatic adenocarcinoma cells and reprogram them toward their original cell type. Thus, pancreatic cancer cells retain a genetic memory which the team state that they hope to exploit. The opensource study is published in the journal Pancreas.
The team generated human pancreatic ductal adenocarcinoma cell lines to make higher than normal levels of E47. The increased amount of E47 caused cells to stall in the G0/G1 growth phase, and differentiate back toward an acinar cell phenotype. In vivo studies showed that when the reprogrammed cancer cells were introduced into mice, their ability to form tumours was greatly diminished compared to untreated adenocarcinoma cells.
The researchers explain that presently, pancreatic adenocarcinoma is treated with cytotoxic agents, yet the average survival for patients post-diagnosis is merely six months, and the improvements in therapies are measured in days. The data findings show that the medical community can differentiate these cancer cells back to a non-threatening phenotype. Indeed, there is a precedent for cell differentiation therapy in that the approach has been used to treat acute promyelocytic leukemia (APL) and some neuroblastomas successfully state the team.
The next step, state the researchers, is to test primary patient-derived tumour tissue to determine whether E47 can produce similar results, potentially providing a novel therapeutic approach to combat this highly lethal disease. Additionally, the team are screening for molecules, potential drugs, that can induce overexpression of E47.